Differential regulation of extracellular matrix constituents in myocardial remodeling with and without heart failure following pressure overload

The aim of the present study was to examine potential differences in the regulation of myocardial ECM constituents, in mice that develop hypertrophy only (ABnonHF) and in mice that develop overt heart failure (ABHF) as response to pressure overload. Seven weeks old male C57BL/6 mice were subjected to aortic banding (AB) or sham operation (sAB), with sacrifice 4 weeks after banding. Prior to sacrifice, cardiac function and geometry were evaluated by echocardiography. Animals with comparable gradients over the banded ascending aorta, comparable cardiac output and heart rate were divided into two groups: ABnonHF and ABHF. Our criterion for dividing AB animals into these two groups was based on lung weight and left atrial diameter (LAD), as an increase in these parameters most likely is due to pulmonary congestion. Heart failure (HF) was defined as an increase in lung weight and LAD defining ABnonHF as lung weight/tibia length ≤ 10.5 mg/mm and LAD ≤ 2.0 mm and ABHF as lung weight/tibia length ≥ 15 mg/mm and LAD ≥ 2.4 mm. Microarray screening was performed in 7 mice from each AB group and in 5 sAB mice. Sham was used as control.

本研究旨在探究仅出现心肌肥厚的小鼠（ABnonHF）与发生显性心力衰竭的小鼠（ABHF）在应对压力超负荷时，其心肌细胞外基质（extracellular matrix, ECM）成分调控方面的潜在差异。实验对象为7周龄雄性C57BL/6小鼠，接受主动脉缩窄（aortic banding, AB）手术或假手术（sham operation, sAB），并于缩窄术后4周实施安乐死。安乐死术前，通过超声心动图评估小鼠的心脏功能与心脏几何形态。将升主动脉缩窄处压力梯度、心输出量及心率均匹配的动物分为ABnonHF与ABHF两组。本研究的分组标准基于肺重量与左心房内径（left atrial diameter, LAD），因上述参数升高多提示肺淤血。心力衰竭（heart failure, HF）的判定标准为肺重量与左心房内径升高：ABnonHF组的判定阈值为肺重量/胫骨长度≤10.5 mg/mm且左心房内径≤2.0 mm；ABHF组的判定阈值为肺重量/胫骨长度≥15 mg/mm且左心房内径≥2.4 mm。本研究对每组AB造模小鼠的7只个体及5只假手术组小鼠进行了微阵列筛查（microarray screening），以假手术组作为对照。